Loss of RUBCN/rubicon in adipocytes mediates the upregulation of autophagy to promote the fasting response
Tadashi Yamamuro, Shuhei Nakamura, Kyosuke Yanagawa, Ayaka Tokumura, Tsuyoshi Kawabata, Atsunori Fukuhara, Hirofumi Teranishi, Maho Hamasaki, Iichiro Shimomura, Tamotsu Yoshimori
Abstract
-knockout mice exhibited systemic fat loss that was not accelerated by fasting. Genetic inhibition of autophagy in adipocytes in fasted mice led to a reduction in fat loss, hepatic steatosis, and ketonemia. In terms of mechanism, autophagy decreased the levels of its substrates NCOA1/SRC-1 and NCOA2/TIF2, which are also coactivators of PPARG/PPARγ, leading to a fasting-induced reduction in the mRNA levels of adipogenic genes in adipocytes. Furthermore, RUBCN in adipocytes was degraded through the autophagy pathway, suggesting that autophagic degradation of RUBCN serves as a feedforward system for autophagy induction during fasting. Collectively, we propose that loss of adipose RUBCN promotes a metabolic response to fasting via increasing autophagic activity.